Prostate cancer has become a major public health problem. In many developed countries it is not only the most commonly diagnosed malignancy but it is the second leading cause of cancer related deaths in males.
Since its discovery more than 20 years ago, prostate specific antigen (PSA) has been the most valuable tool in the detection, staging and monitoring of prostate cancer. Although widely accepted as a prostate tumour marker, PSA is known to be prostate tissue—but not prostate cancer-specific. PSA levels have been reported to increase in men with benign prostatic hyperplasia (BPH) and prostatitis. This substantial overlap in serum PSA values between men with non-malignant prostatic diseases and prostate cancer is the limitation of PSA as a prostate tumour marker. Moreover, a single reading of PSA cannot be used to differentiate the aggressive tumours from the indolent ones. Thus, (non-invasive) molecular tests that can accurately identify those men who have early stage, clinically localized prostate cancer, and who would gain prolonged survival and quality of life from early radical intervention are urgently needed.
Looking for new diagnostic, prognostic markers as well as understanding the molecular mechanisms underlying the disease progress and progression process and identify new treatment targets is the main focus for current prostate cancer research. For the identification of new candidate markers for prostate cancer it is necessary to study expression patterns in malignant as well as non-malignant prostate tissues. One of the genes identified to be overexpressed in prostate cancer is the anterior gradient 2 (AGR2) gene (Bu et al., The Prostate (2011), 575-587). The authors describe long and short transcripts of AGR2 (anterior gradient-2) being up-regulated in prostate cancer cells and tissues. RNAs were isolated from microdissected frozen prostate tissue samples obtained from radical prostatectomy specimens. Total RNA was amplified, reverse transcribed into cDNA and subjected to quantitative real-time PGR. Two transcript variants of the AGR2 gene were detected. Expression of short AGR2 transcript was up-regulated in tumors. Although AGR2 short transcript mRNA level showed slightly higher sensitivity and specificity as compared to the PSA serum level, no significant differences could be observed. Therefore, mRNA level of the AGR2 short transcript in tissue or in the urine sediment are considered as not applicable for a reliable detection of prostate carcinoma.
Nilsson et al., British Journal of Cancer (2009) 100, 1603-1607 analyze prostate cancer-derived urine exosomes as novel approach to biomarkers for prostate cancer. The authors describe the application of urine exosomes as a source for prostate cancer biomarkers. Thereby, mRNA levels of two known prostate cancer biomarkers designated as PCA-3 and TMPRSS2:ERG were tested in several patients. For the detection of corresponding mRNA a prostate massage was applied prior to urine harvesting which is not applicable in routine daily praxis. The article does, however, not provide data about the status of the tumor markers in tumor tissues. Consequently it is not possible to evaluate the diagnostic and/or prognostic values of the suggested biomarkers. A potential enrichment of the two biomarkers PCA-3 and TMPRSS2:ERG in urine exosomes seems to be at least questionable. Since the article shows only slightly higher specificity and sensitivity for prostate cancer detection as compared to the frequently used PSA serum level the test described in this article does not seem promising for the implementation into daily clinical routine.